Linaclotide is a peptide that is useful as an agonist of the guanylate cyclase C (GC-C) receptor in the treatment of gastrointestinal disorders. Linaclotide is described, for example, in U.S. Pat. Nos. 7,304,036 and 7,371,727, the contents of which are incorporated herein by reference in their entirety.
There is an existing and continual need for linaclotide formulations, for example, low-dose and pediatric formulations, having improved stability and performance. This need arises in part because of the intrinsic and chemical instability of linaclotide (for example, induced by moisture-driven degradation reactions such as hydrolysis, deamidation, isomerization, and multimerization). These difficulties may be exacerbated when producing pediatric formulations and other low-dose formulations of linaclotide, e.g., because the linaclotide is more dispersed and has greater surface area exposure to aqueous environments such as during preparation.
The present invention provides such improved stability formulations of linaclotide. These formulations are described herein.